Affiliation:
1. Department of Genetics, University of Washington, Seattle, Washington 98195-7360
Abstract
ABSTRACT
In this report we describe experiments to investigate a simple virulence model in which
Pseudomonas aeruginosa
PAO1 rapidly paralyzes and kills the nematode
Caenorhabditis elegans
. Our results imply that hydrogen cyanide is the sole or primary toxic factor produced by
P. aeruginosa
that is responsible for killing of the nematode. Four lines of evidence support this conclusion. First, a transposon insertion mutation in a gene encoding a subunit of hydrogen cyanide synthase (
hcnC
) eliminated nematode killing. Second, the 17 avirulent mutants examined all exhibited reduced cyanide synthesis, and the residual production levels correlated with killing efficiency. Third, exposure to exogenous cyanide alone at levels comparable to the level produced by PAO1 killed nematodes with kinetics similar to those observed with bacteria. The killing was not enhanced if
hcnC
mutant bacteria were present during cyanide exposure. And fourth, a nematode mutant (
egl-9
) resistant to
P. aeruginosa
was also resistant to killing by exogenous cyanide in the absence of bacteria. A model for nematode killing based on inhibition of mitochondrial cytochrome oxidase is presented. The action of cyanide helps account for the unusually broad host range of virulence of
P. aeruginosa
and may contribute to the pathogenesis in opportunistic human infections due to the bacterium.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
376 articles.
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